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2. Hospital-level volume in extracorporeal membrane oxygenation cases and death or disability at 6 months

Author

Hodgson, Carol, Fulcher, Bentley, Linke, Natalie, Board, Jasmin, Buhr, Heidi, Cooper, Jamie, Fraser, John, Bernard, Stephen, Brodie, Daniel, Pilcher, David, Fan, Eddy, Udy, Andrew, Gattas, David, Pellegrino, Vincent, Hopper, Ingrid, Litton, Ed, Nair, Priya, Orford, Neil, Parke, Rachael, Stub, Dion, Higgins, Alisa M., Burrell, Aidan, McGuiness, Shay, Reddi, Benjamin, Trapani, Tony, Huckson, Sue, Anderson, Shannah, Dicker, Craig, Jones, Annalie, Martin, Emma, McCracken, Phoebe, Sheldrake, Jayne, Vallance, Shirley, Young, Meredith, Bellomo, Rinaldo, Eastwood, Glenn, Hilton, Andrew, Peck, Leah, Dyett, John, Hunter, Stephanie, Liew, Cheelim, Heard, Joshua, Lijo, Sebastian, Nourse, Mary, Rai, Sumeet, Singh, Manoj, Veerendra, Hemanth, Xu, Tina, Barrett, Jonathan, Brooks, Kyle, Hanlon, Gabrielle, Allen, Chris, Bizzell, Samantha, Eroglu, Ege, Palermo, Annamaria, Pellicano, Susan, Bersten, Andrew, Bihari, Shailesh, Brown, Julia, Comerford, Sharon, Grear, Laura, McIntyre, Joanne, Jin, Xia, Wiersema, Ubbo, Figures, Dee, Gough, Maimoonbe, Pitman, Julie, Tallott, Mandy, Winearls, James, Brieva, Jorge, Hopkins, Madeleine, Jayarman, Nanda, Poulter, Amber-Louise, Quarello, Kate, Aneman, Anders, Austin, Danielle, McCanny, Peter, Miller, Jennene, Murfin, Brendan, Cox, Yolanda, Guo, Stephanie, Shehabi, Yayha, Brown, Amanda, Butt, Pamela, Bushell, Rachel, Lavana, Jayshree, Lockwood, Dawn, Pearce, India, Salt, Gavin, Thambiraj, Solomon, Howard, Meg, Joyce, Chris, Meyer, Jason, Walsham, James, Brown, Nerissa, Glasby, Kathleen, O'Connor, Stephanie, Rivett, Justine, Yap, Joannies, Bristow, Debra, Pincus, Jason, Stuart, Janine, Anstey, James, Barge, Deborah, Butler, Menoly, Gebbie, Bradley, Bass, Frances, Janin, Pierre, Hammond, Naomi, Potger, Kieron, Yarad, Elizabeth, Carey, Ruaidhri, Coles, Jennifer, Totaro, Richard, Anstey, Matthew, Endemann, Anthadene, Hardy, Sarah, Popa, Roxana, Richards, Stephen, Rock, Lara, Wibrow, Bradley, Barbazza, Leanne, Dixon, Barry, Holmes, Jennifer, Hurune, Patricia, O'Brien, Yvette, Buscher, Hergen, Newman, Sally, Reynolds, Claire, Henson, Gail, Senthuran, Siva, Win, April, Breguet, Samantha, Horton, Michelle, McCaffrey, Joe, Trickey, Jemma, Bannerjee, Ashoke, Davidson, Benjamin, Joy, Jenyfer, Kong, Jing, Ertugrul, Atacan D., Neto, Ary Serpa, Fulcher, Bentley J., Charles-Nelson, Anaïs, Bailey, Michael, Burrell, Aidan J.C., Board, Jasmin V., Cooper, D. James, Fraser, John F., Gattas, David J., Hopper, Ingrid K., Linke, Natalie J., Litton, Edward, McGuinness, Shay P., Parke, Rachael L., Pellegrino, Vincent A., Pilcher, David V., Udy, Andrew A., Reddi, Benjamin A.J., Trapani, Tony V., and Hodgson, Carol L.

Published
2024
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4. Low-dose clonidine infusion to improve sleep in postoperative patients in the high dependency unit: a randomised placebo controlled trial

Author

Liu, David, primary, Hallt, Elizabeth, additional, Platz, Alanna, additional, Humblet, Alain, additional, Lassig-Smith, Melissa, additional, Stuart, Janine, additional, Fourie, Cheryl, additional, Livermore, Amelia, additional, McConnochie, Bre-Yana, additional, Herbst, Kimberley, additional, Woods, Christine A., additional, Pincus, Jason M., additional, and Reade, Michael Charles, additional

Published
2024
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5. Hospital-level volume in extracorporeal membrane oxygenation cases and death or disability at 6 months

Author

Ertugrul, Atacan D., Neto, Ary Serpa, Fulcher, Bentley J., Charles-Nelson, Anaïs, Bailey, Michael, Burrell, Aidan J.C., Anderson, Shannah, Bernard, Stephen, Board, Jasmin V., Brodie, Daniel, Buhr, Heidi, Cooper, D. James, Dicker, Craig, Fan, Eddy, Fraser, John F., Gattas, David J., Hopper, Ingrid K., Huckson, Sue, Linke, Natalie J., Litton, Edward, McGuinness, Shay P., Nair, Priya, Orford, Neil, Parke, Rachael L., Pellegrino, Vincent A., Pilcher, David V., Stub, Dion, Udy, Andrew A., Reddi, Benjamin A.J., Trapani, Tony V., Jones, Annalie, Higgins, Alisa M., Hodgson, Carol L., Hodgson, Carol, Fulcher, Bentley, Linke, Natalie, Board, Jasmin, Buhr, Heidi, Cooper, Jamie, Fraser, John, Bernard, Stephen, Brodie, Daniel, Pilcher, David, Fan, Eddy, Udy, Andrew, Gattas, David, Pellegrino, Vincent, Hopper, Ingrid, Litton, Ed, Nair, Priya, Orford, Neil, Parke, Rachael, Stub, Dion, Higgins, Alisa M., Burrell, Aidan, McGuiness, Shay, Reddi, Benjamin, Trapani, Tony, Huckson, Sue, Anderson, Shannah, Dicker, Craig, Jones, Annalie, Board, Jasmin, Jones, Annalie, Martin, Emma, McCracken, Phoebe, Pellegrino, Vincent, Sheldrake, Jayne, Vallance, Shirley, Young, Meredith, Bellomo, Rinaldo, Eastwood, Glenn, Hilton, Andrew, Peck, Leah, Dyett, John, Hunter, Stephanie, Liew, Cheelim, Heard, Joshua, Lijo, Sebastian, Nourse, Mary, Rai, Sumeet, Singh, Manoj, Veerendra, Hemanth, Xu, Tina, Barrett, Jonathan, Brooks, Kyle, Hanlon, Gabrielle, Allen, Chris, Bizzell, Samantha, Eroglu, Ege, Litton, Ed, Palermo, Annamaria, Pellicano, Susan, Bersten, Andrew, Bihari, Shailesh, Brown, Julia, Comerford, Sharon, Grear, Laura, McIntyre, Joanne, Jin, Xia, Wiersema, Ubbo, Figures, Dee, Gough, Maimoonbe, Pitman, Julie, Tallott, Mandy, Winearls, James, Brieva, Jorge, Hopkins, Madeleine, Jayarman, Nanda, Poulter, Amber-Louise, Quarello, Kate, Aneman, Anders, Austin, Danielle, McCanny, Peter, Miller, Jennene, Murfin, Brendan, Cox, Yolanda, Guo, Stephanie, Shehabi, Yayha, Brown, Amanda, Butt, Pamela, Bushell, Rachel, Fraser, John, Lavana, Jayshree, Lockwood, Dawn, Pearce, India, Salt, Gavin, Thambiraj, Solomon, Howard, Meg, Joyce, Chris, Meyer, Jason, Walsham, James, Brown, Nerissa, Glasby, Kathleen, O'Connor, Stephanie, Reddi, Benjamin, Rivett, Justine, Yap, Joannies, Bristow, Debra, Pincus, Jason, Stuart, Janine, Anstey, James, Barge, Deborah, Butler, Menoly, Gebbie, Bradley, Bass, Frances, Janin, Pierre, Hammond, Naomi, Potger, Kieron, Yarad, Elizabeth, Buhr, Heidi, Carey, Ruaidhri, Coles, Jennifer, Gattas, David, Totaro, Richard, Anstey, Matthew, Endemann, Anthadene, Hardy, Sarah, Popa, Roxana, Richards, Stephen, Rock, Lara, Wibrow, Bradley, Barbazza, Leanne, Dixon, Barry, Holmes, Jennifer, Hurune, Patricia, O'Brien, Yvette, Buscher, Hergen, Nair, Priya, Newman, Sally, Reynolds, Claire, Henson, Gail, Senthuran, Siva, Win, April, Breguet, Samantha, Horton, Michelle, McCaffrey, Joe, Orford, Neil, Trickey, Jemma, Bannerjee, Ashoke, Davidson, Benjamin, Joy, Jenyfer, and Kong, Jing

Abstract

Extracorporeal membrane oxygenation (ECMO) is a high-risk procedure with significant morbidity and mortality and there is an uncertain volume-outcome relationship, especially regarding long-term functional outcomes. The aim of this study was to examine the association between ECMO centre volume and long-term death and disability outcomes.

Published
2024
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7. Association between augmented renal clearance and clinical outcomes in patients receiving β-lactam antibiotic therapy by continuous or intermittent infusion: a nested cohort study of the BLING-II randomised, placebo-controlled, clinical trial

Author

Bellomo, Rinaldo, Eastwood, Glenn, Peck, Leah, Young, Helen, Boschert, Catherine, Fletcher, Jason, Smith, Julie, Nand, Kiran, Sara, Treena, Shirwadkar, Charudatt, Harney, Amy, Rodgers, Helen, Van Haren, Frank, Clarke, Sally, Durham, David, Hannan, Catherine, Matheson, Elisha, Schwartz, Kate, Thomas, Karen, Bone, Allison, Cattigan, Claire, Elderkin, Tania, Salerno, Tania, Cameron, Robert, Ellis, Katrina, Hatter, Sheridan, Davis, Joshua, Sanap, Milind, Soar, Natalie, Wood, Josette, Chan, Karen, Heffernan, Aaron, Lai, Nai An, Moss, Catherine, Sheehy, Kate, Duroux, Maree, Ratcliffe, Megan, Shone, Samantha, Warhurst, Timothy, Dulhunty, Joel, Dunlop, Rachel, Lipman, Jeffrey, Paterson, David, Roberts, Jason, Starr, Therese, Stuart, Janine, Udy, Andrew, Cooper, David, McAllister, Rick, Webb, Steve, Cheng, Andrew, Inskip, Deborah, Miller, Jennene, Myburgh, John, Knowles, Serena, Reynolds, Claire, Rudham, Sam, Baker, Stuart, Hepburn, Kristy, Roberts, Brigit, Woods, Paul, Chatterjee, Indranil, Smith, Judy, Cullen, Martin, Kong, Jing, Nayyar, Vineet, Whitehead, Christina, Gomersall, Charles, Leung, Patricia, Gilder, Eileen, McCarthy, Lianne, McGuiness, Shay, Parke, Rachael, Benefield, Kirsten, Chen, Yan, McArthur, Colin, Newby, Lynette, Henderson, Seton, Mehrtens, Jan, Noble, Sascha, Chadwick, Lesley, Freebain, Ross, Hogan, Chantal, Kazemi, Alex, Rust, Laura, Song, Rima, Tilsley, Anna, Williams, Anthony, Durning, John, Frengley, Robert, La Pine, Mary, McCracken, Geoff, Sharma, Swarna Baskar, Andrews, Lynn, Dinsdale, Richard, Hunt, Anna, Hurford, Sally, Mackle, Diane, Ongley, Jessica, Young, Paul, Kollef, Marin, Turnidge, John, Paul, Sanjoy, Udy, Andrew A., Dulhunty, Joel M., Roberts, Jason A., Davis, Joshua S., Webb, Steven A.R., Eastwood, Glenn M., Paterson, David L., and Paul, Sanjoy K.

Published
2017
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8. Is inhaled prophylactic heparin useful for prevention and Management of Pneumonia in ventilated ICU patients?: The IPHIVAP investigators of the Australian and New Zealand Intensive Care Society Clinical Trials Group

Author

Bandeshe, Hiran, Boots, Rob, Dulhunty, Joel, Dunlop, Rachael, Holley, Anthony, Jarrett, Paul, Gomersall, Charles D., Lipman, Jeff, Lo, Thomas, O'Donoghue, Steven, Paratz, Jenny, Paterson, David, Roberts, Jason A., Starr, Therese, Stephens, Di, Stuart, Janine, Thomas, Jane, Udy, Andrew, and White, Hayden

Published
2016
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10. PREdiction and Diagnosis using Imaging and Clinical biomarkers Trial in Traumatic Brain Injury (PREDICT-TBI) study protocol: an observational, prospective, multicentre cohort study for the prediction of outcome in moderate-to-severe TBI

Author

Nasrallah, Fatima, primary, Bellapart, Judith, additional, Walsham, James, additional, Jacobson, Esther, additional, To, Xuan Vinh, additional, Manzanero, Silvia, additional, Brown, Nathan, additional, Meyer, Jason, additional, Stuart, Janine, additional, Evans, Tracey, additional, Chandra, Shekhar S, additional, Ross, Jason, additional, Campbell, Lewis, additional, Senthuran, Siva, additional, Newcombe, Virginia, additional, McCullough, James, additional, Fleming, Jennifer, additional, Pollard, Clifford, additional, and Reade, Michael, additional

Published
2023
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12. Diagnostic Sensitivity of Plasma Endothelin-1 for Cerebral Vasospasm After Subarachnoid Hemorrhage, a Multicentre Double-Blind Study

Author

Bellapart, Judith, Nasrallah, Fatima, Winearls, James, Lassig-Smith, Melissa, Stuart, Janine, Boots, Rob, Winter, Craig, Flaws, Dylan, Bulmer, Andrew, Jones, Lee, Laupland, Kevin BjØrn, Bellapart, Judith, Nasrallah, Fatima, Winearls, James, Lassig-Smith, Melissa, Stuart, Janine, Boots, Rob, Winter, Craig, Flaws, Dylan, Bulmer, Andrew, Jones, Lee, and Laupland, Kevin BjØrn

Abstract

The purpose of this study is to establish the diagnostic sensitivity of Endothelin-1 for risk stratification and screening of clinical vasospasm after subarachnoid hemorrhage. This is a multicentre, observational study, correlating daily blood Endothelin-1 with clinical variables. Binary logistic regression used to examine if Endothelin-1 levels could be used to predict clinical vasospasm. Bivariate modelling used to explore associations between patient characteristics and vasospasm. A Receiver Operating Curve used to explore cut-off values for Endothelin-1. Sensitivity and specificity was used to validate the cut-point found in the pilot study. A total of 96 patients were enrolled over two years. Median Endothelin-1 was higher for patients who experienced clinical vasospasm except for day-5, where median endothelin for patients without vasospasm was higher (3.6 IQR = 5.3), compared to patients with vasospasm (3.3 IQR = 8.5) although differences were not significant. The Receiver Operating Curve analysis confirmed that day-5 Endothelin-1 was not a good indicator of vasospasm, with an area under the curve of 0.506 (95% CI: 0.350-0.663, p = 0.938). The levels of Endothelin-1 in blood do not discriminate patients who may develop symptomatic vasospasm. The high variability in Endothelin-1 levels, aligns with the pathophysiological variability of most biomarkers, decreasing their ability to predict a clinical event.

Published
2022

13. Diagnostic Sensitivity of Plasma Endothelin-1 for Cerebral Vasospasm After Subarachnoid Hemorrhage, a Multicentre Double-Blind Study

Author

Bellapart, Judith, primary, Nasrallah, Fatima, additional, Winearls, James, additional, Lassig-Smith, Melissa, additional, Stuart, Janine, additional, Boots, Rob, additional, Winter, Craig, additional, Flaws, Dylan, additional, Bulmer, Andrew, additional, Jones, Lee, additional, and Laupland, Kevin BjØrn, additional

Published
2021
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14. A comparative assessment of two conservative methods for the diagnosis of catheter-related infection in critically ill patients

Author

Gowardman, John R., Jeffries, Paula, Lassig-Smith, Melissa, Stuart, Janine, Jarrett, Paul, Deans, Renae, and McGrail, Matthew

Subjects
Diagnosis, Comparative analysis, Methods, Health aspects, Catheterization -- Methods -- Comparative analysis -- Health aspects, Blood tests -- Methods -- Comparative analysis -- Health aspects, Medical research -- Comparative analysis -- Methods -- Health aspects, Infection -- Diagnosis, Blood -- Medical examination, Medicine, Experimental -- Comparative analysis -- Methods -- Health aspects
Abstract

Author(s): John R. Gowardman [sup.1] [sup.2] [sup.3] [sup.4] [sup.8], Paula Jeffries [sup.1], Melissa Lassig-Smith [sup.1], Janine Stuart [sup.1], Paul Jarrett [sup.1], Renae Deans [sup.1], Matthew McGrail [sup.5], Narelle M. George [...], Purpose To assess the utility of two in situ techniques, differential time to positivity (DTP) and semiquantitative superficial cultures (SQSC) for diagnosing catheter-related bloodstream infection (CR-BSI) in critically ill adults. Methods This was a prospective cohort study in patients with suspected CR-BSI arising from a short-term arterial catheter (AC) or a central venous catheter (CVC). On suspicion of CR-BSI, devices were removed. Blood, skin, catheter tip and hub cultures were taken. Infection rates were compared against the diagnosis of CR-BSI using matched tip and blood cultures. Results Of 120 episodes of clinically suspected CR-BSI in 101 patients examined, 9 (7.5 %) were confirmed as CR-BSI. Validity values (95 % CI) for the diagnosis of CR-BSI arising from both AC and CVC for DTP were: sensitivity 44 % (15-77 %), specificity 98 % (93-100 %), positive predictive value (PPV) 67 % (24-94 %), negative predictive value (NPV) 96 % (90-98 %), positive likelihood ratio (LR+) 25 (5-117), negative likelihood ratio (LR-) 0.6 (0.3-1.0), diagnostic odds ratio (DOR) 44 (7-258), and accuracy 94 % (92-98 %). Validity values (95 % CI) for SQSC were: sensitivity 78 % (41-96 %), specificity 60 % (50-69 %), PPV 14 % (6-26 %), NPV 97 % (89-99 %), LR+ 1.9 (1.0-2.3), LR- 0.4 (0.1-1.3), DOR 5.1 (1.1-19), and accuracy 61 % (51-69 %). DTP combined with SQSC improved sensitivity and NPV to 100 % whilst the DOR increased to 25.8 (95 % CI 3-454). Conclusions CR-BSI can be ruled out by undertaking DTP and SQSC concurrently for both ACs and CVCs with 100 % sensitivity and NPV.

Published
2013
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16. sj-docx-2-jicm-10.1177_08850666211056568 - Supplemental material for Diagnostic Sensitivity of Plasma Endothelin-1 for Cerebral Vasospasm After Subarachnoid Hemorrhage, a Multicentre Double-Blind Study

Author

Bellapart, Judith, Nasrallah, Fatima, Winearls, James, Lassig-Smith, Melissa, Stuart, Janine, Boots, Rob, Winter, Craig, Flaws, Dylan, Bulmer, Andrew, Jones, Lee, and Laupland, Kevin Bj��rn

Subjects
110203 Respiratory Diseases, FOS: Clinical medicine, 111702 Aged Health Care, FOS: Health sciences, 110305 Emergency Medicine
Abstract

Supplemental material, sj-docx-2-jicm-10.1177_08850666211056568 for Diagnostic Sensitivity of Plasma Endothelin-1 for Cerebral Vasospasm After Subarachnoid Hemorrhage, a Multicentre Double-Blind Study by Judith Bellapart, Fatima Nasrallah, James Winearls, Melissa Lassig-Smith, Janine Stuart, Rob Boots, Craig Winter, Dylan Flaws, Andrew Bulmer, Lee Jones and Kevin Bj��rn Laupland in Journal of Intensive Care Medicine

Published
2021
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17. sj-docx-1-jicm-10.1177_08850666211056568 - Supplemental material for Diagnostic Sensitivity of Plasma Endothelin-1 for Cerebral Vasospasm After Subarachnoid Hemorrhage, a Multicentre Double-Blind Study

Author

Bellapart, Judith, Nasrallah, Fatima, Winearls, James, Lassig-Smith, Melissa, Stuart, Janine, Boots, Rob, Winter, Craig, Flaws, Dylan, Bulmer, Andrew, Jones, Lee, and Laupland, Kevin Bj��rn

Subjects
110203 Respiratory Diseases, FOS: Clinical medicine, 111702 Aged Health Care, FOS: Health sciences, 110305 Emergency Medicine
Abstract

Supplemental material, sj-docx-1-jicm-10.1177_08850666211056568 for Diagnostic Sensitivity of Plasma Endothelin-1 for Cerebral Vasospasm After Subarachnoid Hemorrhage, a Multicentre Double-Blind Study by Judith Bellapart, Fatima Nasrallah, James Winearls, Melissa Lassig-Smith, Janine Stuart, Rob Boots, Craig Winter, Dylan Flaws, Andrew Bulmer, Lee Jones and Kevin Bj��rn Laupland in Journal of Intensive Care Medicine

Published
2021
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21. A validated LC-MS/MS method for the simultaneous quantification of the novel combination antibiotic, ceftolozane–tazobactam, in plasma (total and unbound), CSF, urine and renal replacement therapy effluent: application to pilot pharmacokinetic studies

Author

Parker, Suzanne L., primary, Pandey, Saurabh, additional, Sime, Fekade B., additional, Stuart, Janine, additional, Lipman, Jeffrey, additional, Roberts, Jason A., additional, and Wallis, Steven C., additional

Published
2020
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27. A validated LC-MS/MS method for the simultaneous quantification of the novel combination antibiotic, ceftolozane–tazobactam, in plasma (total and unbound), CSF, urine and renal replacement therapy effluent: application to pilot pharmacokinetic studies

Author

Parker, Suzanne L., Pandey, Saurabh, Sime, Fekade B., Stuart, Janine, Lipman, Jeffrey, Roberts, Jason A., and Wallis, Steven C.

Subjects
RENAL replacement therapy, CEREBROSPINAL fluid, TANDEM mass spectrometry, ANTIBIOTICS, MATRIX effect, PILOT projects, INTERFERON beta 1b, COLISTIN
Abstract

Novel treatment options for some carbapenem-resistant Gram-negative pathogens have been identified by the World Health Organization as being of the highest priority. Ceftolozane–tazobactam is a novel cephalosporin–beta-lactamase inhibitor combination antibiotic with potent bactericidal activity against the most difficult-to-treat multi-drug resistant and extensively drug resistant Gram-negative pathogens. This study aimed to develop and validate a liquid chromatography – tandem mass spectrometry method for the simultaneous quantification of ceftolozane and tazobactam in plasma (total and unbound), renal replacement therapy effluent (RRTE), cerebrospinal fluid (CSF) and urine. Analytes were separated using mixed-mode chromatography with an intrinsically base-deactivated C18 column and a gradient mobile phase consisting of 0.1% formic acid, 10 mM ammonium formate and acetonitrile. The analytes and internal standards were detected using rapid ionisation switching between positive and negative modes with simultaneous selected reaction monitoring. A quadratic calibration was obtained for plasma (total and unbound), RRTE and CSF over the concentration range of 1–200 mg/L for ceftolozane and 0.5–100 mg/L for tazobactam, and for urine the concentration range of 10–2,000 mg/L for ceftolozane and 5–1,000 mg/L for tazobactam. For both ceftolozane and tazobactam, validation testing for matrix effects, precision and accuracy, specificity and stability were all within the acceptance criteria of ±15%. This methodology was successfully applied to one pilot pharmacokinetic study in infected critically ill patients, including patients receiving renal replacement therapy, and one case study of a patient with ventriculitis, where all patients received ceftolozane–tazobactam. [ABSTRACT FROM AUTHOR]

Published
2021
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29. Association between augmented renal clearance and clinical outcomes in patients receiving β-lactam antibiotic therapy by continuous or intermittent infusion: a nested cohort study of the BLING-II randomised, placebo-controlled, clinical trial

Author

Udy, Andrew A., primary, Dulhunty, Joel M., additional, Roberts, Jason A., additional, Davis, Joshua S., additional, Webb, Steven A.R., additional, Bellomo, Rinaldo, additional, Gomersall, Charles, additional, Shirwadkar, Charudatt, additional, Eastwood, Glenn M., additional, Myburgh, John, additional, Paterson, David L., additional, Starr, Therese, additional, Paul, Sanjoy K., additional, Lipman, Jeffrey, additional, Eastwood, Glenn, additional, Peck, Leah, additional, Young, Helen, additional, Boschert, Catherine, additional, Fletcher, Jason, additional, Smith, Julie, additional, Nand, Kiran, additional, Sara, Treena, additional, Harney, Amy, additional, Rodgers, Helen, additional, Van Haren, Frank, additional, Clarke, Sally, additional, Durham, David, additional, Hannan, Catherine, additional, Matheson, Elisha, additional, Schwartz, Kate, additional, Thomas, Karen, additional, Bone, Allison, additional, Cattigan, Claire, additional, Elderkin, Tania, additional, Salerno, Tania, additional, Cameron, Robert, additional, Ellis, Katrina, additional, Hatter, Sheridan, additional, Davis, Joshua, additional, Sanap, Milind, additional, Soar, Natalie, additional, Wood, Josette, additional, Chan, Karen, additional, Heffernan, Aaron, additional, Lai, Nai An, additional, Moss, Catherine, additional, Sheehy, Kate, additional, Duroux, Maree, additional, Ratcliffe, Megan, additional, Shone, Samantha, additional, Warhurst, Timothy, additional, Dulhunty, Joel, additional, Dunlop, Rachel, additional, Paterson, David, additional, Roberts, Jason, additional, Stuart, Janine, additional, Udy, Andrew, additional, Cooper, David, additional, McAllister, Rick, additional, Webb, Steve, additional, Cheng, Andrew, additional, Inskip, Deborah, additional, Miller, Jennene, additional, Knowles, Serena, additional, Reynolds, Claire, additional, Rudham, Sam, additional, Baker, Stuart, additional, Hepburn, Kristy, additional, Roberts, Brigit, additional, Woods, Paul, additional, Chatterjee, Indranil, additional, Smith, Judy, additional, Cullen, Martin, additional, Kong, Jing, additional, Nayyar, Vineet, additional, Whitehead, Christina, additional, Leung, Patricia, additional, Gilder, Eileen, additional, McCarthy, Lianne, additional, McGuiness, Shay, additional, Parke, Rachael, additional, Benefield, Kirsten, additional, Chen, Yan, additional, McArthur, Colin, additional, Newby, Lynette, additional, Henderson, Seton, additional, Mehrtens, Jan, additional, Noble, Sascha, additional, Chadwick, Lesley, additional, Freebain, Ross, additional, Hogan, Chantal, additional, Kazemi, Alex, additional, Rust, Laura, additional, Song, Rima, additional, Tilsley, Anna, additional, Williams, Anthony, additional, Durning, John, additional, Frengley, Robert, additional, La Pine, Mary, additional, McCracken, Geoff, additional, Sharma, Swarna Baskar, additional, Andrews, Lynn, additional, Dinsdale, Richard, additional, Hunt, Anna, additional, Hurford, Sally, additional, Mackle, Diane, additional, Ongley, Jessica, additional, Young, Paul, additional, Kollef, Marin, additional, Turnidge, John, additional, and Paul, Sanjoy, additional

Published
2017
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30. Population pharmacokinetics of piperacillin in nonobese, obese, and morbidly obese critically ill patients

Author

Alobaid, Abdulaziz, Wallis, Steven, Jarrett, Paul, Starr, Therese, Stuart, Janine, Lassig-Smith, Melissa, Ordonez Mejia, Jenny Lisette, Roberts, Michael, Roger, Claire, Udy, Andrew, Lipman, Jeffrey, Roberts, Jason, Alobaid, Abdulaziz, Wallis, Steven, Jarrett, Paul, Starr, Therese, Stuart, Janine, Lassig-Smith, Melissa, Ordonez Mejia, Jenny Lisette, Roberts, Michael, Roger, Claire, Udy, Andrew, Lipman, Jeffrey, and Roberts, Jason

Abstract

Free to read on publisher's website The treatment of infections in critically ill obese and morbidly obese patients is challenging because of the combined physiological changes that result from obesity and critical illness. The aim of this study was to describe the population pharmacokinetics of piperacillin in a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients who received piperacillin-tazobactam were classified according to their body mass index (BMI) as nonobese, obese, and morbidly obese. Plasma samples were collected, and piperacillin concentrations were determined by a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were performed using Pmetrics software. Thirty-seven critically ill patients (including 12 obese patients and 12 morbidly obese patients) were enrolled. The patients' mean ± standard deviation age, weight, and BMI were 50 ± 15 years, 104 ± 35 kg, and 38.0 ± 15.0 kg/m2, respectively. The concentration-time data were best described by a two-compartment linear model. The mean ± SD parameter estimates for the final covariate model were a clearance of 14.0 ± 7.1 liters/h, a volume of distribution of the central compartment of 49.0 ± 19.0 liters, an intercompartmental clearance from the central compartment to the peripheral compartment of 0.9 ± 0.6 liters · h−1, and an intercompartmental clearance from the peripheral compartment to the central compartment of 2.3 ± 2.8 liters · h−1. A higher measured creatinine clearance and shorter-duration infusions were associated with a lower likelihood of achieving therapeutic piperacillin exposures in patients in all BMI categories. Piperacillin pharmacokinetics are altered in the presence of obesity and critical illness. As with nonobese patients, prolonged infusions increase the likelihood of achieving therapeutic concentrations.

Published
2017

31. Population Pharmacokinetics of Piperacillin in Nonobese, Obese, and Morbidly Obese Critically Ill Patients

Author

Alobaid, Abdulaziz S., primary, Wallis, Steven C., additional, Jarrett, Paul, additional, Starr, Therese, additional, Stuart, Janine, additional, Lassig-Smith, Melissa, additional, Mejia, Jenny Lisette Ordóñez, additional, Roberts, Michael S., additional, Roger, Claire, additional, Udy, Andrew A., additional, Lipman, Jeffrey, additional, and Roberts, Jason A., additional

Published
2017
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32. Augmented Renal Clearance in Traumatic Brain Injury: A Single-Center Observational Study of Atrial Natriuretic Peptide, Cardiac Output, and Creatinine Clearance

Author

Udy, Andrew A., primary, Jarrett, Paul, additional, Lassig-Smith, Melissa, additional, Stuart, Janine, additional, Starr, Therese, additional, Dunlop, Rachel, additional, Deans, Renae, additional, Roberts, Jason A., additional, Senthuran, Siva, additional, Boots, Robert, additional, Bisht, Kavita, additional, Bulmer, Andrew C., additional, and Lipman, Jeffrey, additional

Published
2017
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33. Effect of obesity on the population pharmacokinetics of meropenem in critically ill patients

Author

Alobaid, Abdulaziz, Wallis, Steven, Jarrett, Paul, Starr, Therese, Stuart, Janine, Lassig-Smith, Melissa, Ordonez Mejia, Jenny Lisette, Roberts, Michael, Lipman, Jeffrey, Roberts, Jason, Alobaid, Abdulaziz, Wallis, Steven, Jarrett, Paul, Starr, Therese, Stuart, Janine, Lassig-Smith, Melissa, Ordonez Mejia, Jenny Lisette, Roberts, Michael, Lipman, Jeffrey, and Roberts, Jason

Abstract

Severe pathophysiological changes in critical illness can lead to dramatically altered antimicrobial pharmacokinetics (PK). The additional effect of obesity on PK potentially increases the challenge for effective dosing. The aim of this prospective study was to describe the population PK of meropenem for a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients prescribed meropenem were recruited into the following three body mass index (BMI) groups: nonobese (18.5 to 29.9 kg/m2), obese (30.0 to 39.9 kg/m2), and morbidly obese (≥40 kg/m2). Serial plasma samples were taken, and meropenem concentrations were determined using a validated chromatographic method. Population PK analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Nineteen critically ill patients with different BMI categories were enrolled. The patients' mean ± standard deviation (SD) age, weight, and BMI were 49 ± 15.9 years, 95 ± 22.0 kg, and 33 ± 7.0 kg/m2, respectively. A two-compartment model described the data adequately. The mean ± SD parameter estimates for the final covariate model were as follows: clearance (CL), 15.5 ± 6.0 liters/h; volume of distribution in the central compartment (V1), 11.7 ± 5.8 liters; intercompartmental clearance from the central compartment to the peripheral compartment, 25.6 ± 35.1 liters h-1; and intercompartmental clearance from the peripheral compartment to the central compartment, 8.32 ± 12.24 liters h-1. Higher creatinine clearance (CLCR) was associated with a lower probability of target attainment, with BMI having little effect. Although obesity was found to be associated with an increased V1, dose adjustment based on CLCR appears to be more important than patient BMI.

Published
2016

34. Effect of obesity on the population pharmacokinetics of fluconazole in critically ill patients

Author

Alobaid, Abdulaziz, Wallis, Steven, Jarrett, Paul, Starr, Therese, Stuart, Janine, Lassig-Smith, Melissa, Ordonez Mejia, Jenny Lisette, Roberts, Michael, Sinnollareddy, Mahipal, Roger, Claire, Lipman, Jeffrey, Roberts, Jason, Alobaid, Abdulaziz, Wallis, Steven, Jarrett, Paul, Starr, Therese, Stuart, Janine, Lassig-Smith, Melissa, Ordonez Mejia, Jenny Lisette, Roberts, Michael, Sinnollareddy, Mahipal, Roger, Claire, Lipman, Jeffrey, and Roberts, Jason

Abstract

Our objective was to describe the population pharmacokinetics of fluconazole in a cohort of critically ill nonobese, obese, and morbidly obese patients. Critically ill patients prescribed fluconazole were recruited into three body mass index (BMI) cohorts, nonobese (18.5 to 29.9 kg/m2), obese (30.0 to 39.9 kg/m2), and morbidly obese (≥40 kg/m2). Serial fluconazole concentrations were determined using a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Twenty-one critically ill patients (11 male) were enrolled, including obese (n = 6) and morbidly obese (n = 4) patients. The patients mean ± standard deviation (SD) age, weight, and BMI were 54 ± 15 years, 90 ± 24 kg, and 31 ± 9 kg/m2, respectively. A two-compartment linear model described the data adequately. The mean ± SD population pharmacokinetic parameter estimates were clearance (CL) of 0.95 ± 0.48 liter/h, volume of distribution of the central compartment (Vc) of 15.10 ± 11.78 liter, intercompartmental clearance from the central to peripheral compartment of 5.41 ± 2.28 liter/h, and intercompartmental clearance from the peripheral to central compartment of 2.92 ± 4.95 liter/h. A fluconazole dose of 200 mg daily was insufficient to achieve an area under the concentration-time curve for the free, unbound drug fraction/MIC ratio of 100 for pathogens with MICs of ≥2 mg/liter in patients with BMI of >30 kg/m2. A fluconazole loading dose of 12 mg/kg and maintenance dose of 6 mg/kg/day achieved pharmacodynamic targets for higher MICs. A weight-based loading dose of 12 mg/kg followed by a daily maintenance dose of 6 mg/kg, according to renal function, is required in critically ill patients for pathogens with a MIC of 2 mg/liter.

Published
2016

35. Effect of Obesity on the Population Pharmacokinetics of Fluconazole in Critically Ill Patients

Author

Alobaid, Abdulaziz S., primary, Wallis, Steven C., additional, Jarrett, Paul, additional, Starr, Therese, additional, Stuart, Janine, additional, Lassig-Smith, Melissa, additional, Mejia, Jenny Lisette Ordóñez, additional, Roberts, Michael S., additional, Sinnollareddy, Mahipal G., additional, Roger, Claire, additional, Lipman, Jeffrey, additional, and Roberts, Jason A., additional

Published
2016
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36. Erratum to “Is inhaled prophylactic heparin useful for prevention and management of pneumonia in ventilated ICU patients? The IPHIVAP investigators of the Australian and New Zealand Intensive Care Society Clinical Trials Group” Journal of Critical Care 34 (2016) 95–102

Author

Bandeshe, Hiran, primary, Boots, Rob, additional, Dulhunty, Joel, additional, Dunlop, Rachael, additional, Holley, Anthony, additional, Jarrett, Paul, additional, Gomersall, Charles D., additional, Lipman, Jeff, additional, Lo, Thomas, additional, O'Donoghue, Steven, additional, Paratz, Jenny, additional, Paterson, David, additional, Roberts, Jason A., additional, Starr, Therese, additional, Stephens, Di, additional, Stuart, Janine, additional, Thomas, Jane, additional, Udy, Andrew, additional, and White, Hayden, additional

Published
2016
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38. Glucocorticoid Sensitivity Is Highly Variable in Critically Ill Patients With Septic Shock and Is Associated With Disease Severity*

Author

Cohen, Jeremy, primary, Pretorius, Carel J., additional, Ungerer, Jacobus P. J., additional, Cardinal, John, additional, Blumenthal, Antje, additional, Presneill, Jeff, additional, Gatica-Andrades, Marcela, additional, Jarrett, Paul, additional, Lassig-Smith, Melissa, additional, Stuart, Janine, additional, Dunlop, Rachel, additional, Starr, Therese, additional, and Venkatesh, Bala, additional

Published
2016
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39. Doripenem population pharmacokinetics and dosing requirements for critically ill patients receiving continuous venovenous haemodiafiltration

Author

Roberts, Jason, Udy, Andrew, Bulitta, Juergen, Stuart, Janine, Jarrett, Paul, Starr, Therese, Lassig-Smith, Melissa, Roberts, Natasha, Dunlop, Rachel, Hayashi, Yoshiro, Wallis, Steven, Lipman, Jeffrey, Roberts, Jason, Udy, Andrew, Bulitta, Juergen, Stuart, Janine, Jarrett, Paul, Starr, Therese, Lassig-Smith, Melissa, Roberts, Natasha, Dunlop, Rachel, Hayashi, Yoshiro, Wallis, Steven, and Lipman, Jeffrey

Abstract

Free to read on publisher's website Objectives Doripenem is a newer carbapenem with little data available to guide effective dosing during renal replacement therapy in critically ill patients. The objective of this study was to determine the population pharmacokinetics of doripenem in critically ill patients undergoing continuous venovenous haemodiafiltration (CVVHDF) for acute kidney injury (AKI). Methods This was an observational pharmacokinetic study in 12 infected critically ill adult patients with AKI undergoing CVVHDF and receiving 500 mg of doripenem intravenously every 8 h as a 60 min infusion. Serial blood samples were taken on 2 days of treatment and used for population pharmacokinetic analysis with S-ADAPT. Results The median (IQR) age was 62 (53–71) years, the median (IQR) weight was 77 (67–96) kg and the median (IQR) APACHE II score was 29 (19–32). The median blood, dialysate and replacement fluid rates were 200, 1000 and 1000 mL/h, respectively. A two-compartment linear model with doripenem clearance described by CVVHDF, renal or non-renal mechanisms was most appropriate. The mean value for total doripenem clearance was 4.46 L/h and volume of distribution was 38.0 L. Doripenem clearance by CVVHDF was significantly correlated with the replacement fluid flow rate and accounted for ∼30%–37% of total clearance. A dose of 500 mg intravenously every 8 h achieved favourable pharmacokinetic/pharmacodynamics for all patients up to an MIC of 4 mg/L. Conclusions This is the first paper describing the pharmacokinetics/pharmacodynamics of doripenem in critically ill patients with AKI receiving CVVHDF. A dose of 500 mg intravenously every 8 h was appropriate for our CVVHDF settings for infections caused by susceptible bacteria.

Published
2014

41. A comparative assessment of two conservative methods for the diagnosis of catheter-related infection in critically ill patients

Author

Gowardman, John, Jeffries, Paula, Lassig-Smith, Melissa, Stuart, Janine, Jarrett, Paul, Deans, Renae, McGrail, Matthew, George, Narelle, Nimmo, Graeme, Rickard, Claire, Gowardman, John, Jeffries, Paula, Lassig-Smith, Melissa, Stuart, Janine, Jarrett, Paul, Deans, Renae, McGrail, Matthew, George, Narelle, Nimmo, Graeme, and Rickard, Claire

Abstract

Purpose To assess the utility of two in situ techniques, differential time to positivity (DTP) and semiquantitative superficial cultures (SQSC) for diagnosing catheter-related bloodstream infection (CR-BSI) in critically ill adults. Methods This was a prospective cohort study in patients with suspected CR-BSI arising from a short-term arterial catheter (AC) or a central venous catheter (CVC). On suspicion of CR-BSI, devices were removed. Blood, skin, catheter tip and hub cultures were taken. Infection rates were compared against the diagnosis of CR-BSI using matched tip and blood cultures. Results Of 120 episodes of clinically suspected CR-BSI in 101 patients examined, 9 (7.5 %) were confirmed as CR-BSI. Validity values (95 % CI) for the diagnosis of CR-BSI arising from both AC and CVC for DTP were: sensitivity 44 % (15–77 %), specificity 98 % (93–100 %), positive predictive value (PPV) 67 % (24–94 %), negative predictive value (NPV) 96 % (90–98 %), positive likelihood ratio (LR+) 25 (5–117), negative likelihood ratio (LR−) 0.6 (0.3–1.0), diagnostic odds ratio (DOR) 44 (7–258), and accuracy 94 % (92–98 %). Validity values (95 % CI) for SQSC were: sensitivity 78 % (41–96 %), specificity 60 % (50–69 %), PPV 14 % (6–26 %), NPV 97 % (89–99 %), LR+ 1.9 (1.0–2.3), LR− 0.4 (0.1–1.3), DOR 5.1 (1.1–19), and accuracy 61 % (51–69 %). DTP combined with SQSC improved sensitivity and NPV to 100 % whilst the DOR increased to 25.8 (95 % CI 3–454). Conclusions CR-BSI can be ruled out by undertaking DTP and SQSC concurrently for both ACs and CVCs with 100 % sensitivity and NPV.

Published
2013

42. Plasma and tissue pharmacokinetics of cefazolin in patients undergoing elective and semielective abdominal aortic aneurysm open repair surgery

Author

Douglas, Alexandra, Udy, Andrew, Wallis, Steven, Jarrett, Paul, Stuart, Janine, Lassig-Smith, Melissa, Deans, Renae, Roberts, Michael, Taraporewalla, Kersi, Jenkins, Jason, Medley, Gregory, Lipman, Jeffrey, Roberts, Jason, Douglas, Alexandra, Udy, Andrew, Wallis, Steven, Jarrett, Paul, Stuart, Janine, Lassig-Smith, Melissa, Deans, Renae, Roberts, Michael, Taraporewalla, Kersi, Jenkins, Jason, Medley, Gregory, Lipman, Jeffrey, and Roberts, Jason

Abstract

Free to read on publisher's website Surgical site infections are common, so effective antibiotic concentrations at the sites of infection, i.e., in the interstitial fluid (ISF), are required. The aim of this study was to evaluate contemporary perioperative prophylactic dosing of cefazolin by determining plasma and subcutaneous ISF concentrations in patients undergoing elective/semielective abdominal aortic aneurysm (AAA) open repair surgery. This was a prospective pharmacokinetic study in a tertiary referral hospital. Cefazolin (2 g) was administered as a 3-min slow bolus 30 min prior to incision in 12 enrolled patients undergoing elective/semielective AAA open repair surgery. Serial blood, urine, and ISF (via microdialysis) samples were collected and analyzed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Cardiac output was determined using pulse waveform contours with Vigileo. The recruited patients had a median (interquartile range) age of 70 (66 to 76) years and weight of 88 (81 to 95) kg. The median (interquartile range) terminal volume of distribution was 0.14 (0.11 to 0.15) liter/kg, total clearance was 0.05 (0.03 to 0.06) liter/h, and minimum observed unbound concentration was 5.7 (5.4 to 8.1) mg/liter. The penetration of unbound drug from plasma to ISF was 85% (78% to 106%). We found correlations present, albeit weak, between cefazolin clearance and cardiac output (r2 = 0.11) and urinary creatinine clearance (r2 = 0.12). In conclusion, we found that a single 2-g dose of cefazolin administered 30 min before incision provides plasma and ISF concentrations in excess of the likely MICs for susceptible pathogens in patients undergoing AAA open repair surgery.

Published
2011

43. A comparison of CKD-EPI estimated glomerular filtration rate and measured creatinine clearance in recently admitted critically ill patients with normal plasma creatinine concentrations

Author

Udy, Andrew A, primary, Morton, Fraser JA, additional, Nguyen-Pham, Sallyanne, additional, Jarrett, Paul, additional, Lassig-Smith, Melissa, additional, Stuart, Janine, additional, Dunlop, Rachel, additional, Starr, Therese, additional, Boots, Robert J, additional, and Lipman, Jeffrey, additional

Published
2013
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45. Plasma and Tissue Pharmacokinetics of Cefazolin in Patients Undergoing Elective and Semielective Abdominal Aortic Aneurysm Open Repair Surgery

Author

Douglas, Alexandra, primary, Udy, Andrew A., additional, Wallis, Steven C., additional, Jarrett, Paul, additional, Stuart, Janine, additional, Lassig-Smith, Melissa, additional, Deans, Renae, additional, Roberts, Michael S., additional, Taraporewalla, Kersi, additional, Jenkins, Jason, additional, Medley, Gregory, additional, Lipman, Jeffrey, additional, and Roberts, Jason A., additional

Published
2011
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48. Erratum to “Is inhaled prophylactic heparin useful for prevention and management of pneumonia in ventilated ICU patients? The IPHIVAP investigators of the Australian and New Zealand Intensive Care Society Clinical Trials Group” Journal of Critical Care34 (2016) 95–102

Author

Bandeshe, Hiran, Boots, Rob, Dulhunty, Joel, Dunlop, Rachael, Holley, Anthony, Jarrett, Paul, Gomersall, Charles D., Lipman, Jeff, Lo, Thomas, O'Donoghue, Steven, Paratz, Jenny, Paterson, David, Roberts, Jason A., Starr, Therese, Stephens, Di, Stuart, Janine, Thomas, Jane, Udy, Andrew, and White, Hayden

Published
2016
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49. Effect of Obesity on the Population Pharmacokinetics of Fluconazole in Critically Ill Patients

Author

Janine Stuart, Jenny Lisette Ordóñez Mejia, Michael S. Roberts, Jason A. Roberts, Mahipal G. Sinnollareddy, Therese Starr, Abdulaziz S. Alobaid, Melissa Lassig-Smith, Paul Jarrett, Steven C. Wallis, Claire Roger, Jeffrey Lipman, Unité de réanimation médicale [CHU de Carémeau, Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Alobaid, Abdulaziz S, Wallis, Steven C, Jarrett, Paul, Starr, Therese, Stuart, Janine, Lassig-Smith, Melissa, Mejia, Jenny Lisette Ordóñez, Roberts, Michael S, Sinnollareddy, Mahipal G, Roger, Claire, Lipman, Jeffrey, and Roberts, Jason A

Subjects
Male, 0301 basic medicine, Antifungal Agents, Body Mass Index, fluconazole, critically ill nonobese, Pharmacology (medical), Prospective Studies, Fluconazole, Candida, 2. Zero hunger, Volume of distribution, education.field_of_study, Maintenance dose, Candidiasis, Liter, Middle Aged, Obesity, Morbid, 3. Good health, Intensive Care Units, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Area Under Curve, Female, Monte Carlo Method, Adult, medicine.medical_specialty, Critical Illness, 030106 microbiology, Population, Urology, Microbial Sensitivity Tests, Loading dose, Drug Administration Schedule, 03 medical and health sciences, Pharmacokinetics, medicine, Humans, Intensive care medicine, education, Aged, Pharmacology, Models, Statistical, obese, business.industry, morbidly obese patients, Pharmacodynamics, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business, Body mass index
Abstract

Our objective was to describe the population pharmacokinetics of fluconazole in a cohort of critically ill nonobese, obese, and morbidly obese patients. Critically ill patients prescribed fluconazole were recruited into three body mass index (BMI) cohorts, nonobese (18.5 to 29.9 kg/m 2 ), obese (30.0 to 39.9 kg/m 2 ), and morbidly obese (≥40 kg/m 2 ). Serial fluconazole concentrations were determined using a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Twenty-one critically ill patients (11 male) were enrolled, including obese ( n = 6) and morbidly obese ( n = 4) patients. The patients mean ± standard deviation (SD) age, weight, and BMI were 54 ± 15 years, 90 ± 24 kg, and 31 ± 9 kg/m 2 , respectively. A two-compartment linear model described the data adequately. The mean ± SD population pharmacokinetic parameter estimates were clearance (CL) of 0.95 ± 0.48 liter/h, volume of distribution of the central compartment ( V c ) of 15.10 ± 11.78 liter, intercompartmental clearance from the central to peripheral compartment of 5.41 ± 2.28 liter/h, and intercompartmental clearance from the peripheral to central compartment of 2.92 ± 4.95 liter/h. A fluconazole dose of 200 mg daily was insufficient to achieve an area under the concentration-time curve for the free, unbound drug fraction/MIC ratio of 100 for pathogens with MICs of ≥2 mg/liter in patients with BMI of >30 kg/m 2 . A fluconazole loading dose of 12 mg/kg and maintenance dose of 6 mg/kg/day achieved pharmacodynamic targets for higher MICs. A weight-based loading dose of 12 mg/kg followed by a daily maintenance dose of 6 mg/kg, according to renal function, is required in critically ill patients for pathogens with a MIC of 2 mg/liter.

Published
2016
Full Text
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50. Plasma and tissue pharmacokinetics of cefazolin in patients undergoing elective and semielective abdominal aortic aneurysm open repair surgery

Author

Melissa Lassig-Smith, Jeffrey Lipman, Andrew A. Udy, Jason A. Roberts, Jason Jenkins, Michael S. Roberts, Gregory Medley, Alexandra Douglas, Renae Deans, Janine Stuart, Paul Jarrett, Kersi Taraporewalla, Steven C. Wallis, Douglas, Alexandra, Udy, Andrew A, Wallis, Steven C, Jarrett, Paul, Stuart, Janine, Lassig-Smith, Melissa, Deans, Renae, Roberts, Michael S, Taraporewalla, Kersi, Jenkins, Jason, Medley, Gregory, Lipman, Jeffrey, and Roberts, Jason A

Subjects
Male, medicine.medical_specialty, Microdialysis, Cefazolin, Renal function, Microbiology, Bolus (medicine), Pharmacokinetics, Interquartile range, Tandem Mass Spectrometry, medicine, Humans, Pharmacology (medical), Prospective Studies, Pharmacology & Pharmacy, repair surgery, plasma, Aged, Volume of distribution, Aged, 80 and over, Pharmacology, business.industry, tissue, Perioperative, Middle Aged, medicine.disease, Abdominal aortic aneurysm, Surgery, Infectious Diseases, Elective Surgical Procedures, Anesthesia, cefazolin, Female, business, medicine.drug, Aortic Aneurysm, Abdominal
Abstract

Surgical site infections are common, so effective antibiotic concentrations at the sites of infection, i.e., in the interstitial fluid (ISF), are required. The aim of this study was to evaluate contemporary perioperative prophylactic dosing of cefazolin by determining plasma and subcutaneous ISF concentrations in patients undergoing elective/semielective abdominal aortic aneurysm (AAA) open repair surgery. This was a prospective pharmacokinetic study in a tertiary referral hospital. Cefazolin (2 g) was administered as a 3-min slow bolus 30 min prior to incision in 12 enrolled patients undergoing elective/semielective AAA open repair surgery. Serial blood, urine, and ISF (via microdialysis) samples were collected and analyzed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Cardiac output was determined using pulse waveform contours with Vigileo. The recruited patients had a median (interquartile range) age of 70 (66 to 76) years and weight of 88 (81 to 95) kg. The median (interquartile range) terminal volume of distribution was 0.14 (0.11 to 0.15) liter/kg, total clearance was 0.05 (0.03 to 0.06) liter/h, and minimum observed unbound concentration was 5.7 (5.4 to 8.1) mg/liter. The penetration of unbound drug from plasma to ISF was 85% (78% to 106%). We found correlations present, albeit weak, between cefazolin clearance and cardiac output ( r 2 = 0.11) and urinary creatinine clearance ( r 2 = 0.12). In conclusion, we found that a single 2-g dose of cefazolin administered 30 min before incision provides plasma and ISF concentrations in excess of the likely MICs for susceptible pathogens in patients undergoing AAA open repair surgery.

Published
2011

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